End-Stage Diastolic and Systolic Heart Failure: Evaluation and Timing of Heart Transplantation

Abstract

End-stage hypertrophic cardiomyopathy occurs in an estimated 3–15% of patients and can present as either systolic or diastolic dysfunction. Risk factors for developing end-stage disease include a family history of end-stage disease, younger age at initial diagnosis, increased wall thickness, persistent arrhythmias, and high scar burden on MRI. The classic form of adverse remodeling includes left ventricular cavity dilation with regression of hypertrophy, wall thinning, and decrease in ejection fraction. Standard medical therapy for systolic heart failure and consideration of prophylactic defibrillator is indicated when LVEF is less than 50%. Heart transplant is a viable option for patients with end-stage hypertrophic cardiomyopathy, including those with systolic heart failure, diastolic heart failure, or refractory arrhythmias. Strategies used to bridge patients to transplant include continuous inotropic infusion, left ventricular assist device, intra-aortic balloon pump, and in rare cases extracorporeal membrane oxygenation. Survival after heart transplantation for hypertrophic cardiomyopathy is equal to or better than survival for patients who have other types of cardiomyopathies.

Questions

• 1. Which of the following is an indication for heart transplantation (HT) in a patient with hypertrophic cardiomyopathy?

  • A. Severe heart failure symptoms unresponsive to medical therapy in the setting of normal systolic function

  • B. Severe heart failure symptoms unresponsive to medical therapy in the setting of reduced systolic function

  • C. Severe left ventricular outflow tract obstruction

  • D. Massive left ventricular hypertrophy

  • E. A and B

  Answer: E. Heart failure that is severe and unresponsive is an indication for OHT regardless of whether there is reduced or preserved systolic function. A LVOT obstruction should be treated with specific therapies that relieve that obstruction (such as septal reduction therapy and medications) and the symptoms it may be causing. Massive LVH by itself is not an indication for OHT; other factors (heart failure symptoms, uncontrolled ventricular tachycardia, and/or persistent symptoms of ischemia) need to be present for transplant to be considered.

• 2. Which statement is true regarding long-term outcomes in HT in adult patients with HCM?

  • A. Median survival is less than that for those undergoing HT for ischemic cardiomyopathy.

  • B. Average survival is less than 10 years.

  • C. Median survival is at least as good as that for non-HCM patients who are transplanted.

  • D. HCM tends to recur in the transplanted heart.

  • E. There is a higher incidence of graft rejection in HCM patients after transplantation.

  Answer: C. Data from single center reports, multicenter databases, and large transplant databases suggest that survival in HCM patients after transplantation is excellent and is better than those who had ischemic CM and similar to those with nonischemic DCM. Average survival appears better than the overall 11-year average survival of all transplant patients. Although LVH may occur in the transplanted heart from a variety of factors (hypertension, rejection, ischemia, calcineurin inhibitor use), HCM does not recur in the transplanted heart. The incidence of graft rejection is not increased in HCM patients compared to other non-HCM patients who have been transplanted.

• 3. Transplantation in the HCM population is characterized by which of the following:

  • A. HCM is a common indication for HT.

  • B. Most HCM patients will need to be considered for HT.

  • C. HCM patients undergoing HT are, on average, older than non-HCM patients undergoing HT.

  • D. HCM patients tend to have longer wait times on the HT list.

  • E. LVEFs are lower, and LV cavities are larger in HCM patients being considered for HT compared to non-HCM patients.

  Answer: D. Patients with HCM who are listed for OHT tend to have longer waiting times for transplantation. This seems to be driven primarily by patients who have preserved LVEF who are not candidates for therapies that elevated transplant status such as inotropes and LVADs . HCM is not a common indication for OHT (<2–3% of all transplants are for HCM), and most transplant patients will not progress to need OHT (perhaps 1–2% of all HCM patients). HCM patients who are transplanted are generally younger than the average of non-HCM patients who are transplanted. This is likely influenced by the older age of patients with ischemic CM who undergo OHT.

• 4. HT in pediatric HCM patients differs from that in adults in which of the following ways:

  • A. There is a lower overall survival in pediatric patients.

  • B. There is more frequent use of LVADs in the adult HCM population.

  • C. ECMO is used more often prior to HT in children.

  • D. Pediatric patients more frequently have normal LVEFs and restrictive physiology.

  • E. All of the above.

  Answer: E. All these statements are true. There is greater use of ECMO use and lower use of LVADs in the pediatric population due to anatomical constraints related to patient size and higher incidence of small LV cavity size, normal LVEF, and restrictive physiology in children. Survival after transplant in pediatric patients is lower, primarily due to a much higher mortality in those who are less than 1 year of age.

• 5. A 50-year-old man with HCM has increasing dyspnea and fatigue that do not respond to medical therapy. His LV is mildly dilated and his LVEF is 40%. He is placed on the HT waiting list but continues to clinically decline. Which of the following therapies could be considered as strategies for bridging to HT ?

  • A. LVAD

  • B. Continuous inotrope infusion

  • C. Intra-aortic balloon pump (IABP)

  • D. Total artificial heart

  • E. All of the above

  Answer: E. For the patient with reduced LVEF, all of these strategies can be considered. However, for the patient with preserved LVEF, the use of VADs and inotropes, and possibly IABPs, is more challenging and possibly detrimental. Total artificial heart placement may be a better approach in the HCM patient with normal LVEF in need of advanced mechanical therapies to bridge to transplant.

• 6. Left ventricular assist devices as a means of circulatory support are problematic in many patients with HCM due to all of the following except:

  • A. Small LV cavity size

  • B. Apical hypertrophy

  • C. Mitral regurgitation

  • D. Normal or hyperdynamic LV systolic function

  • E. Hypertrophied, apically displaced papillary muscles

  Answer: C. Mitral regurgitation is not a contraindication for VAD placement. All the other factors may make VAD placement and long-term support and management difficult or impossible. LVADs should generally be avoided in those settings.

• 7. A 35-year-old female with HCM is listed for heart transplant. An extended wait time is anticipated due to blood group and size. LVEF is 45%, and she is being treated with beta blocker, ACE inhibitor, spironolactone, and Lasix. Which of the following is the most appropriate next therapy?

  • A. Biventricular pacing

  • B. Prophylactic defibrillator

  • C. Continuous inotropic therapy

  • D. Hemodialysis

  • E. Sildenafil

  Answer: B. Prophylactic defibrillator is indicated for end-stage HCM when LVEF is <50%. Biventricular pacing has been shown in small studies to have some impact on remodeling parameters in patients with HCM, but no substantive improvement in ejection fraction or survival once listed for transplant. Continuous inotropic therapy can be utilized in selected patients with reduced cardiac output, and sildenafil may be beneficial in patients with elevated pulmonary vascular resistance. There is no need for dialysis in this patient.

• 8. A 65-year-old male with HCM, HTN, and hyperlipidemia reports new symptoms of breathlessness and chest pain. Transthoracic echocardiogram reveals resting left ventricular outflow tract gradient of 25 mmHg and LVEF of 50% which is decreased from 65%. What is the next best step in management?

  • A. Left heart catheterization with coronary angiography

  • B. Initiation of verapamil

  • C. Initiation of diuretic therapy

  • D. Implantation of prophylactic ICD

  • E. Uptitration of beta blocker dose

  Answer: A. In patients with HCM who develop new systolic dysfunction, other cardiac disorders should be ruled out. This patient has risk factors for CAD including HTN and hyperlipidemia and is presenting with new breathlessness and chest pain. Coronary angiography with left heart catheterization to measure LVOT gradient will provide the best hemodynamic and anatomic assessment. Stress testing may also be considered with careful attention to background medical therapy as beta blockers may interfere with assessment of ischemia in exercise testing. Changes in medical therapy should be guided by the underlying cause of systolic dysfunction. Prophylactic defibrillator may be indicated if LVEF remains <50% once reversible causes are treated.

• 9. Long-standing restrictive cardiac physiology can result in which of the following?

  • A. Biatrial enlargement

  • B. Congestive hepatopathy

  • C. Cardioembolic disease

  • D. Pulmonary hypertension

  • E. All of the above

  Answer: E. Long-standing restrictive cardiac physiology can lead to chronically elevated biventricular filling pressures, adverse remodeling of the atria, atrial thrombus formation, and thromboembolic disease. Congestive hepatopathy and frank cirrhosis can develop if right atrial pressure is elevated chronically, with or without tricuspid regurgitation. Similarly, pulmonary vascular disease can progress with long-standing elevation of left-sided filling pressures.

• 10. A patient with history of obstructive HCM has progressed to end-stage disease with LVEF of 35% and fluid retention. There is no longer LVOT obstruction by echocardiogram. Peak VO₂ = 13 mL/kg/min, respiratory quotient = 1.2. Right heart catheterization reveals RA 11 mmHg, mean PA 27 mmHg, PCW 19 mmHg, CI 2.0 L/min/m², and pulmonary artery saturation 58%. Which of the following is appropriate medical management?

  • A. Discontinue diuretic.

  • B. Uptitrate disopyramide.

  • C. Discontinue verapamil.

  • D. Referral to transplant center.

  • E. C and D.

  Answer: E. In this patient who has a reduced LVEF, marginal cardiac index, and severely reduced functional capacity as evidenced by CPET, it is appropriate to discontinue negative inotropic agents and start transplant evaluation. Diuretics should be continued for symptomatic congestion.

• 11. A 54-year-old female with HCM presents with worsening exercise tolerance. Exam is notable for perioral cyanosis, elevated jugular venous pressure, and palpable liver. TTE reveals no obstruction and LVEF of 60% with biatrial enlargement. BNP is elevated. Six-minute walk distance = 300 m. What is the next best step in management?

  • A. Increase beta blocker dose.

  • B. Order pulmonary function testing.

  • C. Start ACE inhibitor.

  • D. Right heart catheterization.

  • E. Add digoxin.

  Answer: D. This patient is presenting with volume overload and marginal cardiac output as evidenced by elevated venous pressure, palpable liver edge, and cyanosis. Right heart catheterization should be done to evaluate hemodynamics. Normal LVEF with biatrial enlargement and elevated BNP are concerning for restrictive phenotype of end-stage disease.